Our ongoing in vivo and in vitro studies of functionally important cellular populations and of the role of individual proteins in effector functions of T-lymphocytes have obvious immunopharmacological implications since they identify the cell types and key proteins that should be targeted for efficient immunomodulation when there is a clinical need to inhibit or to enhance the intensity of the effector phase of the immune response. A. Synthetic peptides inhibitors/pseudosubstrates of protein kinases as modulators of T-lymphocyte responses. We tested if it is possible to use peptides which mimic pseudosubstrate sequences or inhibitory domains of known protein kinases and demonstrated that such peptides are able to block functional responses of T-cells. Some peptides were only inhibitory, while PKA-inhibiting synthetic peptide was able to enhance the 1CR- triggered IL2 production of T-cells when directly delivered in the cytoplasm by hypotonic shock. The advantages of this synthetic peptide- based strategy for immunomodulation include the possibility of the rational design of individual peptides according to the defined properties of the targeted enzymes, achieving both biochemical and, hopefully, cell- specific specificity of novel inhibitors. B. The differential modulation of cytotoxic T cells effector functions. During the systematic studies of the effects of different enzyme inhibitors, anti-sense mRNA oligos and of different synthetic peptide inhibitors on lymphocyte functions we succeed in demonstration of the possibility to simultaneously inhibit some functions (e.g. gamma- interferon secretion) and to enhance other functions of the same cell (e.g. the cytotoxic "lethal hit" delivery and granule exocytosis) by TCR- triggered CTL by interfering with the activities of serine/threonine PP2A phosphatase and of protein kinase A. This forms the basis for the development of the immunomodulating reagents which will selectively affect the partial reactions of the immune response.